A SUPERVISED ANALYSIS OF GENE-EXPRESSION PROFILES OF PURIFIED CLONAL PLASMA CELLS FROM PATIENTS WITH SYSTEMIC LIGHT-CHAIN AMYLOIDOSIS (AL) WHO HAVE HIGH OR LOW LEVELS OF SERUM FREE LAMBDA LIGHT CHAINS

摘要

Proteins that are secreted by mammalian cells enter the secretory pathway at translation as they are made on polyribosomes attached to the endoplasmic reticulum (ER) membrane. The protein enters the ER as a polypeptide and interacts with chaperones and enzymes as it folds and undergoes post-translational modification. Immunoglobulin light-chains made by plasma cells have two domains, a variable and constant, both of which can fold independently into compact globular structures stabilized by intradomain disulfide bonds between C41 and C109 (variable region) and C156 and C215 (constant region) (1,2). Thermodynamic instability has been associated with light chains that can form amyloid fibrils (3,4). Plasma cells make an excess of light chains and normally secrete small amounts because the light chains are more adept or competent at folding for secretion than heavy chains; heavy chains unassociated with light chains have a hydrophobic area that impairs folding and secretion (1).